A new method for finding compounds to prevent aging
Aging refers to a natural phenomenon that as age increases, the self-tissue structure will gradually undergo degenerative changes, the function of body organs will decline, the ability of internal environment self-stability will be weakened, and the resistance to internal and external environmental damage factors will be reduced, and the body will tend to die. Aging is an inevitable process for all organisms, and human lifespan is directly related to aging.
Human aging is often accompanied by a variety of age-related high-risk diseases such as Alzheimer's disease, diabetes, cardiovascular disease, and cancer. The acceleration of global aging will cause many social problems. Delaying the process of aging and eliminating potential risk factors for aging diseases are imminent. Therefore, prevention of aging through drugs is a valuable research direction that helps people have a healthier, longer-lived life.
Finding substances to prevent aging is a difficult and challenging process. On the one hand, experiments on mammals are expensive and time-consuming. On the other hand, using cultured human cells, more substances can be tested, but aging is a complex process that is difficult to measure at the cellular level.
A study led by researchers at the Karolinska Institute in Sweden supported this idea. The study, published in Cell Reports, reported that by using a new method, the researchers discovered a set of candidate substances that are predicted to revitalize human cells, prolong life, and improve the health of animal model C. elegans.
Researchers use a new method based on interpreting cellular information, especially the so-called transcriptome. A transcriptome represents information about all RNA present in a particular cell or tissue at a given time. Recently, it has been shown that the transcriptome of human cells can be used to predict the age of a person from which a cell is derived. In this way, cell culture systems can be used to understand how different substances affect the biological age of cells.
Because of its short life span (about 2 to 3 weeks) and its ability to serve as a ready-made genetic research tool, C. elegans is often the best biological model for investigating aging in the body. C. elegans have many core metabolic pathways and key factors that very similar to humans. These factors play a key role in determining the lifespan of C. elegans.
Researchers developed their methods through extensive transcriptome data. Through machine-learning methods, they built a classifier that distinguishes transcriptomes from "young" and "old" donors.
The classifier was used to analyze changes in the transcriptome of human cells induced by more than 1,300 substances. In this way, researchers hoped to find substances that can turn the human transcriptome into a "young" age. This method identified several candidate substances, including substances already known to extend the lifespan of different organisms and new candidate substances.
In a further study of C. elegans, the team discovered that Monorden and Tanespimycin blocked an inhibitor of a protein called heat shock protein 90 (Hsp90)
to extend the lifespan of C. elegans. The ability that these two substances appeared is not previously demonstrated. In addition to extending life, Mondoren also improved the health of C. elegans.
The researchers noted that these substances work by activating a protein called heat shock transcription factor 1 (Hsf1)
. Hsf1 is known to result in the expression of so-called chaperone proteins, which enhance the ability of animals to fold their proteins correctly and thus be functional throughout their lifetime.
Researchers have now identified Hsp90 inhibitors as new promising candidates. Hsp90 inhibitors have been tested for other therapeutic purposes and further research is needed on their effects on human aging.